This invention relates to a formulation of composite phytopharmaceuticals containing gel prepared using natural gel like materials and or biocompatible medical grade silicon base coated on porous and breathable matrix of polyurethane or cotton to be used for the treatment of wounds and ulcers in humans and animals. It also relates to the formulation of transdermal patches for delivery of the phytopharmaceuticals. The invention comprises the properties of anti-inflammatory, anti-oxidant, anti-microbial, anti-cancer and wound healing potentials. Further, the invention also comprises useful for Alzheimer's and multiple sclerosis.
The use of wound dressings to cover and protect wounds is very well known. Preferably, the wound dressing should provide a sterile environment at the wound site and should rapidly absorb wound exudates while maintaining a moist wound surface. The dressing should interfere as little as possible with wound healing and should be easy to remove and replace with minimal trauma. Finally, the wound dressing should be inexpensive to make, compact and conformable to all skin surfaces.
The process of wound healing consists of three phases during which the injured tissue is repaired, regenerated, and new tissue is reorganized into a scar. The fibroblasts, endothelial cells, and epithelial cells migrate in the wound site. These fibroblasts produce the collagen that is necessary for wound repair. In re-epithelialization, epithelial cells migrate from the free edges of the tissue across the wound. This event is succeeded by the proliferation of epithelial cells at the periphery of the wound. Research has also shown that re-epithelialization is enhanced by the presence of occlusive wound dressings which maintain a moisture barrier.
A large variety of treatment and modalities are available for the treatment of wounds and ulcers as described here. These range from applications of antibiotics, occlusive layers, bandages, poultices, mechanical devices that reduce evaporation of water and many others. However, all of these modalities have one drawback in common; they all enhance wound healing by supporting the body mechanisms to heal the wound. Unfortunately, the passive healing process results in much disappointment because the body may have compromised immunity or other body functions that may not work optimally. What is needed is a modality of treatment that will actively regenerate the skin, dermis and epidermis. In the invention described here, the specific composition actively promotes healing by stimulating stem cells that are present even in deep wounds and burns to regenerate the lost tissue. Stem cells are by definition present in all self-renewing tissues. These cells are believed to be long-lived, have a great potential for cell division and are ultimately responsible for the homeostasis of steady-state tissues. Stem cells are normally slow cycling. They can, however, be induced to enter the proliferative pool in response to certain growth stimuli. A number of growth factors have been reported to be useful for modulating stem cell activity. For example, cytokines such as Tumor Necrosis Factor (TNF), Epidermal Growth Factor (EGF), Transforming Growth Factor (TGF) and Interleukin-1 (IL-1) are believed to be useful. Because stem cells are normally slow cycling but proliferate rapidly upon inductive stimulation, they may be attractive targets for cytokines.
Several herbal products have been proposed for the treatment of wounds and ulcers. U.S. Pat. No. 6,133,440 provides a rapid and efficient method for the preparation and isolation of biologically active polysaccharides from Aloe, “Immuno-10” and the use of the polysaccharides as immunostimulating, immunomodulating and wound healing agents. U.S. Pat. No. 6,027,728 comprises a selection of herbal materials with curative effects combined in a powdered form for application to human skin to accomplish skin regeneration, particularly for application to human skin affected with eczema, psoriasis, allergic reactions, inflammatory rash and the like. The process of application is critical to effectiveness of the present invention. The application of the herbal powder to the skin is intended to cause a temporary inflammation.
A variety of other herbal extracts may be included, and the compositions may take the form of a cream or ointment based on ghee, or they may be in a powdered form of suitable for preparing decoctions in hot water. U.S. Pat. No. 5,766,614 is a new burn treatment composition which provides healing to the skin of people who have received burns or are afflicted with other skin complications that require healing. U.S. Pat. No. 6,126,950 relates to a formulation of herbal cream for cracked heels and palms. It is comprised of a natural wax as an emulsifier, extract of Curcuma and the gum of Acacia or Colophonium or Shorea. The gum gives a synergistic effect in binding and healing the skin with natural wound healing herbal extract selected from the aqueous extracts of Curcuma, neem and allantonin.
The herbal gel formulation of the present invention consists of a natural herbal nono-aqueous extract of Curcuma longa, curcumin, non-aqueous extract of Emblica officinalis and Camellia sinensis and silicon and/or Aloe vera gel and or polymers viz. gelatin, collagen, carboxymethyl cellulose, alginate, polyvinyl alcohol, polyvinyl pyrrhilidon or equivalent. The healing property including anti-microbial, anti-inflammatory and anti-oxidant nature of curcumin is well established and gel of Aloe vera and silicon have been used which are also well known for wound management. The used other two extracts viz. Emblica officinalis and Camellia sinensis are also well known for anti-microbial, anti-oxidant and anti-inflammatory potentials including wound healing promoting agents. The synergistic action of Curcuma longa extract, curcumin, Emblica officinalis and Camellia sinensis along with Aloe vera gel and/or silicon quickens the healing, binds the skin and makes it soft and supple. A silicon based composition has been added which enhances the soothing and healing property along with Aloe vera and other composition used. Further, this formulation has been coated on porous and breathable matrix of polyurethane and/or cotton to make it a complete wound dressing solution. Furthermore, these nano-formulations are combined with transdermal patches for transdermal drug delivery devices preferably delivering anti-cancer drug.
The prior art relevant to this invention consists of various wound healing, antimicrobial, anti-oxidant and anti-inflammatory compositions comprised of one or a few of the above ingredients and other herbal and chemical mixtures. Further, it also has got anti-cancer potential.
It is known in the art that skin wound healing may be enhanced by the topical application of vitamin, herbal and/or chemical compositions to the affected area or through the ingestion of some such compositions. However, existing inventions inadequately address the need for a therapeutic composition that is all natural, provides fast pain relief, and acts as anti-microbial and anti-oxidants, reduces inflammation and enhances the healing of wounds and ulcers; and also acts as anti-cancer agents.
U.S. Pat. No. 5,466,542 is a pharmaceutical composition for the treatment of skin disorders comprised of extracts of herbs to provide an anti-inflammatory agent, an adrenocortical stimulant and a cortisol protecting agent. U.S. Pat. No. 5,648,380 is a therapeutic anti-inflammatory wound healing composition comprised of an anti-inflammatory agent and a wound healing composition. The wound healing composition is comprised of pyruvate, an antioxidant and a mixture of saturated and unsaturated fatty acids. The anti-inflammatory agent may be chosen from a group consisting of etodalc, Evening Primrose Oil, salsalate, cortisone and select others. The antioxidant may be chosen from a group consisting of all forms of Vitamin A, Vitamin C, Vitamin E and mixtures thereof. The composition is also comprised of a pharmaceutically acceptable carrier. U.S. Pat. No. 5,663,208 is an anti-fungal wound healing composition with anti-fungal agent comprised of lactic and sorbic acid, terconazole or select others. U.S. Pat. No. 5,652,274 by A. Martin, filed a therapeutic wound healing composition comprised of pryuvate, and antioxidant and a mixture of saturated and unsaturated fatty acids. U.S. Pat. No. 5,916,573 is a topical treatment of the skin, comprised of grape-seed oil, a hydrating agent that may be chosen from a group consisting of Vitamin E oil, Primrose oil and select others, an amino acid and deionized water. U.S. Pat. No. 6,183,761 by D. L. Bissett, filed Mar. 12, 1999, is a composition for regulating skin appearance comprised of a Vitamin B3 compound, a polycyclic compound, flavanones, chalcones, isoflavones, coumarins, chromones, dicomarols, chromanols, sterols, selected others and mixtures thereof. Further reference may be made to Ganta S, Devalapally H, Amiji M. curcumin enhances oral bioavailability and anti-tumor therapeutic efficacy of paclitaxel upon administration in nanoemulsion formulation. J pharm sci 2010; 99: 4630-41. Barik A, Praveen N, Indira Priyadarsini K, Kumar m, mohan h. curcumin loaded hydrogels as probable drug delivery systems. National academy science letters 2005; 28: 383-8. Bisht S, Feldmann G, Soni S, Ravi R, Karikar C, Maitra A, Maitra A. polymeric nanoparticle-encapsulated curcumin (“nanocurcumin”): a novel strategy for human cancer therapy. J nanobiotechnology 2007; 5:3. Curcumin derivatives with improved water solubility compared to curcumin and medicaments containing the same (US20030153512).
As disclosed above, a number of compositions exist, and are composed of herbs, chemicals, and vitamins. However, none of the inventions in prior art teach about a composition which uses the ingredients as provided in present invention and showing efficiency. Therefore, it is very important to provide solutions which can solve the above problems in innovative manner. The present invention provides such solution.
Further, none of the prior art discloses an invention that utilizes a topically administered natural therapeutic composition for the treatment of diseases and wounds comprised of a mixture of nano-curcumin, nano-Emblica and nano-Camellia extract contained in Aloe vera and/or silicon based gel. Further, the same is coated on porous and breathable matrix. Furthermore, same is formulated either in combination or individually as transdermal patch for transdermal drug delivery system for therapy of compromised tissues including cancer therapy. Further, the invention also comprises beneficial use for Alzheimer's and multiple sclerosis.
The invention described here comprises a mixture of four herbs and one synthetic polymer, silicon, which (three out of four herbs) are extracted by soaking in non-aqueous solvent e.g. more than 99% ethanol or different ratio of solvent e.g. 1:2.5 wt/wt of acetone:ethanol and formulated to make it water soluble towards enhancing bioavailability. Further, this formulation has been upgraded in terms of better efficacy by using biopolymeric sandwich model and/or synthetic polymer viz. silicon or both. Polymers may be synthetic of biopolymers. Biopolymers may contain from a source of protein e.g. collagen, gelatin or polyschaccharide e.g. chitosan carboxymethyl cellulose or both.
The phytopharmaceutical preparation of the invention described is meant to relieve pain, provides soothing effect and upon repeated use, has the ability to heal the wounds by providing a moist healing environment and stimulating stem cells to regenerate the lost tissues. The transdermal patch formulated with phytopharmaceutical preparation intended for transdermal delivery system preferably for cancer therapy either individually or combination.
In the present invention, water insoluble curcumin from Curcuma longa, extract of Emblica officinalis and Camillia sinensis have been subjected to physico-chemical treatment to solubilize in water and water soluble nano-sized formulation has been developed to enhance the bioavailability of the bioactive bio-molecules, had inherent water insolubility.
Curcumin is a water insoluble candidate isolated from Curcuma longa, its biological efficacies include anti-tumor, anti-inflammatory and anti-oxidant activities. In addition, curcumin displays therapeutic potential for neurological disorders such as Alzheimer's disease. A promising advantage of curcumin is that it displays minimal side effects in clinical applications as the drug. However, the practical applicability of curcumin is limited due to its low bioavailability which is due to poor aqueous solubility, poor gastrointestinal absorption, efficient first pass metabolism and rapid elimination. Therefore, an efficient drug delivery system is anticipated to be a breakthrough technology for the successful medical application of curcumin. Two main approaches are being employed to increase the bioavailability of curcumin. One strategy is based on the chemical modification of the curcumin molecule into water-soluble derivatives. Curcumin possesses two reactive terminal hydroxyl groups. These water-soluble curcumin derivatives might be patentable and considered as drug candidates. Another strategy is based on the nano-particulate drug delivery system. Many types of blend with nano-particles curcumin using polymers (e.g. PLGA) have been tested as drug delivery carriers. Several patents are lined up for curcumin formulation towards increasing its bioavailability includes US 20070148263, WO 2007103435, U.S. Pat. Nos. 6,063,402, 9,192,644, 9,259,401, 8,759,403, 8,772,265. These nano-particulate drug delivery systems appear to be a promising strategy for curcumin delivery. However, some other claim or report (U.S. Pat. No. 8,785,380) stated about dry curcumin powder suspended in excess water containing with or without hydrocolloids under ultrasound mediated ultrasonication, homogenization or cryogenic grinding and basis for carrier are required but none of them provided water soluble and nano form of curcumin and/or other water insoluble phytochemicals in the same form as like curcumin. In the present invention, using a simple physioco-chemical treatment, the water insoluble bioactive phytopharmaceuticals themselves were in nano sized form and water soluble without adding any polymers or surfactant or emulsifier or any equivalent factors reported as nano-formulators and hydrophilic carriers.
As stated above, similarly the non-aqueous extraction of the Emblica officinalis and Camellia sinensis and other plants or herbs was also water insoluble having potential bioactivities but less bioavailability. In the present invention, we adopted another approach i.e. physico-chemical treatment to make pure water insoluble curcumin and non-aqueous extract (water insoluble) of Emblica officinalis and Camellia sinensis into water soluble and nano-sized without using any polymeric carrier in terms of particulate or fiber or gel. The said physico-chemical treatment includes alteration of the pH at different interval of time and ultra-sonication. Following this, the water-solubilized extracts including curcumin were freeze-dried and further directly dissolved in pure water to get water soluble extract. The nano form of curcumin, phytochemical extract of Emblica officinalis and Camellia sinensis and other medicinal plants can also be obtained by high pressure homogenization followed by freeze-drying and further directly dissolved in pure water to get water soluble extract. Further, this approach has been extended and used to make water soluble to the other poor aqueous soluble or insoluble herbal extracts.
Further, it also provides the solution as anti-cancer, anti-Alzheimers and anti-multiple sclerosis in the form of transdermal patch and/or injectables.